EP0965334B1 - Intubations-Flüssigkeits-Beatmungsmittel - Google Patents

Intubations-Flüssigkeits-Beatmungsmittel Download PDF

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Publication number
EP0965334B1
EP0965334B1 EP99111588A EP99111588A EP0965334B1 EP 0965334 B1 EP0965334 B1 EP 0965334B1 EP 99111588 A EP99111588 A EP 99111588A EP 99111588 A EP99111588 A EP 99111588A EP 0965334 B1 EP0965334 B1 EP 0965334B1
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Prior art keywords
perfluoroalkyl
group
semi
alkanes
chain
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English (en)
French (fr)
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EP0965334A1 (de
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Hasso Meinert
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/02—Halogenated hydrocarbons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/04—Artificial tears; Irrigation solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/23—Preparation of halogenated hydrocarbons by dehalogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
    • C07C17/269—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions of only halogenated hydrocarbons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C17/00—Preparation of halogenated hydrocarbons
    • C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
    • C07C17/272—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions
    • C07C17/275—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by addition reactions of hydrocarbons and halogenated hydrocarbons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C19/00—Acyclic saturated compounds containing halogen atoms
    • C07C19/08—Acyclic saturated compounds containing halogen atoms containing fluorine
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10L—FUELS NOT OTHERWISE PROVIDED FOR; NATURAL GAS; SYNTHETIC NATURAL GAS OBTAINED BY PROCESSES NOT COVERED BY SUBCLASSES C10G, C10K; LIQUEFIED PETROLEUM GAS; ADDING MATERIALS TO FUELS OR FIRES TO REDUCE SMOKE OR UNDESIRABLE DEPOSITS OR TO FACILITATE SOOT REMOVAL; FIRELIGHTERS
    • C10L1/00—Liquid carbonaceous fuels
    • C10L1/10—Liquid carbonaceous fuels containing additives
    • C10L1/14—Organic compounds
    • C10L1/20—Organic compounds containing halogen
    • C10L1/201—Organic compounds containing halogen aliphatic bond
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10L—FUELS NOT OTHERWISE PROVIDED FOR; NATURAL GAS; SYNTHETIC NATURAL GAS OBTAINED BY PROCESSES NOT COVERED BY SUBCLASSES C10G, C10K; LIQUEFIED PETROLEUM GAS; ADDING MATERIALS TO FUELS OR FIRES TO REDUCE SMOKE OR UNDESIRABLE DEPOSITS OR TO FACILITATE SOOT REMOVAL; FIRELIGHTERS
    • C10L1/00—Liquid carbonaceous fuels
    • C10L1/10—Liquid carbonaceous fuels containing additives
    • C10L1/14—Organic compounds
    • C10L1/20—Organic compounds containing halogen
    • C10L1/206—Organic compounds containing halogen macromolecular compounds
    • C10L1/207—Organic compounds containing halogen macromolecular compounds containing halogen with or without hydrogen
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M105/00—Lubricating compositions characterised by the base-material being a non-macromolecular organic compound
    • C10M105/50—Lubricating compositions characterised by the base-material being a non-macromolecular organic compound containing halogen
    • C10M105/52—Lubricating compositions characterised by the base-material being a non-macromolecular organic compound containing halogen containing carbon, hydrogen and halogen only
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M107/00—Lubricating compositions characterised by the base-material being a macromolecular compound
    • C10M107/38—Lubricating compositions characterised by the base-material being a macromolecular compound containing halogen
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M131/00—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing halogen
    • C10M131/02—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing halogen containing carbon, hydrogen and halogen only
    • C10M131/04—Lubricating compositions characterised by the additive being an organic non-macromolecular compound containing halogen containing carbon, hydrogen and halogen only aliphatic
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M147/00—Lubricating compositions characterised by the additive being a macromolecular compound containing halogen
    • C10M147/02—Monomer containing carbon, hydrogen and halogen only
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2211/00—Organic non-macromolecular compounds containing halogen as ingredients in lubricant compositions
    • C10M2211/02—Organic non-macromolecular compounds containing halogen as ingredients in lubricant compositions containing carbon, hydrogen and halogen only
    • C10M2211/022—Organic non-macromolecular compounds containing halogen as ingredients in lubricant compositions containing carbon, hydrogen and halogen only aliphatic
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2211/00—Organic non-macromolecular compounds containing halogen as ingredients in lubricant compositions
    • C10M2211/06—Perfluorinated compounds
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2213/00—Organic macromolecular compounds containing halogen as ingredients in lubricant compositions
    • C10M2213/02—Organic macromolecular compounds containing halogen as ingredients in lubricant compositions obtained from monomers containing carbon, hydrogen and halogen only
    • C—CHEMISTRY; METALLURGY
    • C10—PETROLEUM, GAS OR COKE INDUSTRIES; TECHNICAL GASES CONTAINING CARBON MONOXIDE; FUELS; LUBRICANTS; PEAT
    • C10M—LUBRICATING COMPOSITIONS; USE OF CHEMICAL SUBSTANCES EITHER ALONE OR AS LUBRICATING INGREDIENTS IN A LUBRICATING COMPOSITION
    • C10M2213/00—Organic macromolecular compounds containing halogen as ingredients in lubricant compositions
    • C10M2213/06—Perfluoro polymers
    • C10M2213/062—Polytetrafluoroethylene [PTFE]

Definitions

  • oxygen-saturated liquid perfluorocarbons for example perfluorodecalin
  • perfluorodecalin oxygen-saturated liquid perfluorocarbons
  • these perfluorocarbon is introduced directly into the lungs and thus into the alveolar system via a tube inserted up to the trachea.
  • the respiration is guaranteed by the O 2 enriched or saturated perfluorocarbon, a collapse of the lungs is prevented at the same time.
  • the high density of the perfluorocarbon approximately 1.8-2.0 g / cm 3
  • causes respiration or transport of the O 2 - or CO 2 -transporting medium on the part of the weakened or stressed body is difficult.
  • perfluorohydrocarbones The synthesis of perfluorohydrocarbones is known from [8] in which terminal perfluoroalkyl units are bonded to aliphatic or olefinic groups via a tertiary, triple R F -substituted carbon atom directly or via a - (CH 2 ) - spacer. Two of the R F substituents of the terminal tertiary C atom are always CF 3 groups.
  • the known compounds are used for the production of blood substitutes in the form of aqueous emulsions or as cooling liquids for electronics. Furthermore, the known compounds for liquid breathing and extracircular lung washing in smoke inhalation and other lung diseases are to be used.
  • the use of a semifluorinated alkane is proposed for the production of an intubation liquid respirator and according to claim 5 a device for liquid breathing with an O 2 - or CO 2 -transporting medium from a semifluorinated alkane is proposed.
  • the density of the proposed liquid semifluorinated alkanes is advantageously only about 1.1-1.7 g / cm 3 (25 ° C.).
  • This liquid breathing is also possible for divers with the help of semi-fluorinated alkanes.
  • the product placed in the pulmonary O 2 can via the tube - or CO 2 transporting medium are continuously enriched with a circulatory system by means of an oxygenator with O 2 and freed from CO 2 by means of a corresponding CO 2 -Rückhaltesystems.
  • a diver supplied in this way no longer has to breathe in air or oxygen via compressed air cylinders and exhale used air via a valve system.
  • the valve noise and the escaping gas or air bubbles make the diver discoverable via sensitive sonar systems.
  • the semifluorinated alkanes used have the general formulas R F R H and R F R H R F where R F is a linear or branched perfluoroalkyl group and R H is a linear or branched, saturated hydrocarbon-alkyl group
  • a -CX 2 can also -- Wing and 2 -- play be contained within an alkyl chain and a -CY.
  • the tertiary carbon atom is not directly connected to the neighboring hydrocarbon-alkyl group.
  • connection types are analogous to Perfluorocarbons (compounds consisting only of carbon-fluorine bonds exist) chemically, physically and physiologically inert and therefore non-toxic.
  • linear or branched semi-fluorinated alkanes are also suitable as solvents for medicaments, in particular if they have a relatively high alkyl content, - (CH 2 ) n - or - (CH 2 ) n H or their R H -substituted isomers.
  • the semi-fluorinated diblock or Triblock alkanes are colorless liquids. you will be not from strong acids or bases or oxidizing agents or attacked nucleophiles, neither does a metabolic find or catabolic attack instead.
  • the proposed semi-fluorinated alkanes using effective nonionic surfactants fluorosurfactants, combine with fluorophilic head and hydrophilic tail, ethylene oxide-propylene oxide block polymers, Pluronics® or Phospholipids such as eilezetin or soy lecetin, etc.
  • ionic surfactants with the aid of physical emulsification processes Ultrasonic or Gaulin homogenizers
  • the semifluorinated alkanes are both in perfluorocarbons and derivatives of perfluorocarbons (higher molecular weight perfluorinated ethers, Hostinert®, Fomblin® and others) [1-4] and in hydrocarbons and their derivatives and thereby compounds with higher alkyl group proportions (for example liquid paraffins, silicone oils, fatty acid esters, etc.) soluble.
  • perfluorocarbons and derivatives of perfluorocarbons higher molecular weight perfluorinated ethers, Hostinert®, Fomblin® and others
  • hydrocarbons and their derivatives and thereby compounds with higher alkyl group proportions for example liquid paraffins, silicone oils, fatty acid esters, etc.
  • the semi-fluorinated diblock or triblock alkanes are prepared by reacting perfluoroalkyl iodides with alkenes or ⁇ , ⁇ -dienes, after HI elimination and subsequent hydrogenation using H 2 / Raney nickel in a high pressure process [5] or by hydrogenation using platinum contact [6 ] or obtained using tributyltin hydride [4] (see Appendix: Examples of syntheses of semifluorinated diblock and triblock alkanes).
  • the products obtained for the proposed fields of application can preferably still be highly purified.
  • the semifluorinated alkanes are first treated analogously to [7] with acidic permanganate solution, then they are mixed with a mixture of strong aqueous potassium hydroxide solution (4-8 n), CaO or BaO, and a nucleophilic agent (e.g. secondary amine) 150-180 ° C refluxed for about 72 hours or autoclaved.
  • a nucleophilic agent e.g. secondary amine
  • reaction product is separated from the aqueous alkaline phase, which may also contain alcohol, and the amine phase by means of a separating funnel, treated several times in succession with dilute mineral acid, NaHCO 3 solution, distilled water, anhydrous Na 2 SO 4 and anhydrous CaCl 2 and over one powerful column fractionally distilled.
  • ionizable fluoride is suitable as a quantitative method for the determination of groups which can lead to intramolecular HF elimination or to the exchange of a fluorine atom by means of a nucleophilic agent, if this would be bound in a -CHF group, by means of a nucleophilic agent in the reaction of the sample material with hexamethylenediamine in nonane or dean by heating for several hours at 120-150 ° C, whereby any fluoride released is detected by means of an ion-sensitive electrode.
  • no fluoride ions were detectable after the cleaning process (detection limit for the fluoride concentration ⁇ 10 -5 mol ⁇ l -1 ).
  • the highly purified semi-fluorinated alkanes show no inhibition of proliferation with regard to DNA and protein synthesis on HeLa or Molt4 or HEP 2 cell cultures.
  • the semifluorinated alkanes mentioned can thus be used directly for medical, pharmaceutical and biological purposes.
  • the semifluorinated alkanes mentioned can be very easily by means of biocompatible emulsifiers (natural phospholipids, such as soybean or egg yolkethine or synthetically produced lecithins, or phospholipid mixtures with a proportion of 60- 98% of phosphatidylcholine or ethylene oxide-propylene oxide block polymer, Pluronic®, etc.) with the aid of physical emulsification methods (ultrasonic or Gaulin homogenizer, Ultraturrax disperser) to form stable, aqueous emulsions of the o / w and w / o types Process asymmetrical lamellar aggregates.
  • biocompatible emulsifiers natural phospholipids, such as soybean or egg yolkethine or synthetically produced lecithins, or phospholipid mixtures with a proportion of 60- 98% of phosphatidylcholine or ethylene oxide-propylene oxide block polymer, Pluronic®, etc.
  • the temperature is increased to 80 ° C., while a mixture of 23.7 g (0.05 mol) of C 6 F 13 CH 2 CH 2 I and 60 cm 3 of anhydrous di-n-propyl ether is added dropwise with vigorous stirring within 1 hour , The mixture is then stirred under reflux for 9 hours, then cooled to 10 ° C., hydrolyzed with 100 cm 3 of 5% strength by weight aqueous hydrochloric acid until the excess magnesium has detached. Now the ether phase is separated off and concentrated using a rotary evaporator. The resulting oily residue is mixed with 30 cm 3 of chloroform and left to stand at 0 ° C. for 1 hour. The solid product separated from the mixture is suctioned off and dried in the desicator.
  • the perfluoroalkyl iodide is first formed analogously to Example 9, but then the reduction to the semifluorinated alkane, R F R H or R F R H R F , takes place using palladium-carbon or platinum oxide as a catalyst with hydrogen at 4 bar in an autoclave.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Surgery (AREA)
  • Toxicology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Materials For Medical Uses (AREA)
  • External Artificial Organs (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pyridine Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
EP99111588A 1995-09-29 1996-08-09 Intubations-Flüssigkeits-Beatmungsmittel Expired - Lifetime EP0965334B1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19536504A DE19536504C2 (de) 1995-09-29 1995-09-29 Verwendung fluorierter Alkane
DE19536504 1995-09-29
EP96927711A EP0859751B2 (de) 1995-09-29 1996-08-09 Semifluorierte alkane und ihre verwendung

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
EP96927711A Division EP0859751B2 (de) 1995-09-29 1996-08-09 Semifluorierte alkane und ihre verwendung

Publications (2)

Publication Number Publication Date
EP0965334A1 EP0965334A1 (de) 1999-12-22
EP0965334B1 true EP0965334B1 (de) 2002-03-13

Family

ID=7773697

Family Applications (3)

Application Number Title Priority Date Filing Date
EP99111588A Expired - Lifetime EP0965334B1 (de) 1995-09-29 1996-08-09 Intubations-Flüssigkeits-Beatmungsmittel
EP96927711A Expired - Lifetime EP0859751B2 (de) 1995-09-29 1996-08-09 Semifluorierte alkane und ihre verwendung
EP99105854A Expired - Lifetime EP0965329B1 (de) 1995-09-29 1996-08-09 Dermatikum und Verwendung von semifluorierten Alkanen zur Herstellung von Dermatika

Family Applications After (2)

Application Number Title Priority Date Filing Date
EP96927711A Expired - Lifetime EP0859751B2 (de) 1995-09-29 1996-08-09 Semifluorierte alkane und ihre verwendung
EP99105854A Expired - Lifetime EP0965329B1 (de) 1995-09-29 1996-08-09 Dermatikum und Verwendung von semifluorierten Alkanen zur Herstellung von Dermatika

Country Status (9)

Country Link
US (3) US6262126B1 (ko)
EP (3) EP0965334B1 (ko)
JP (3) JP2000511157A (ko)
KR (3) KR100478789B1 (ko)
AT (3) ATE214589T1 (ko)
CA (3) CA2473393C (ko)
DE (4) DE19536504C2 (ko)
ES (3) ES2174554T3 (ko)
WO (1) WO1997012852A1 (ko)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2110126B1 (de) * 2008-04-18 2011-11-09 Novaliq GmbH Inhalative und instillative Verwendung von semifluorierten Alkanen als Wirkstoffträger im intrapulmonalen Bereich

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19719280C1 (de) * 1997-05-07 1998-09-24 Pharm Pur Gmbh Fluorierte Alkane und ihre Verwendungen
DE19861012A1 (de) 1998-03-18 1999-09-30 Pharm Pur Gmbh Behandlungsmittel für die Ophthalmologie
DE19811683C2 (de) * 1998-03-18 2000-03-23 Pharm Pur Gmbh Behandlungsmittel für die Ophthalmologie
DE19926889B4 (de) 1999-06-12 2005-06-16 Bausch & Lomb Inc. Verwendung eines Gels mit Polyaphronstruktur zur Herstellung eines Implantats
DE19926890C1 (de) 1999-06-12 2000-07-27 Pharm Pur Gmbh Verwendung eines hochfluorierten oligomeren Alkans in der Ophthalmologie
US7357937B2 (en) 2002-09-24 2008-04-15 Therox, Inc. Perfluorocarbon emulsions with non-fluorinated surfactants
DE10336841A1 (de) * 2003-08-11 2005-03-17 Rovi Gmbh & Co. Kosmetische Rohstoffe Kg Kosmetische Zusammensetzung zur Unterstützung des Sauerstofftransports in die Haut
EP1667619A4 (en) * 2003-09-19 2007-10-10 Drugtech Corp PHARMACEUTICAL FEEDING SYSTEM
DE10358306B8 (de) 2003-12-08 2005-03-03 Coty B.V. Kosmetisches und dermatologisches Sauerstoff-Trägersystem, Verfahren zu dessen Herstellung sowie seine Verwendung
JP2008501032A (ja) * 2004-06-01 2008-01-17 ザ・トラスティーズ・オブ・コロンビア・ユニバーシティ・イン・ザ・シティ・オブ・ニューヨーク 眼内を長期タンポナーデするための部分的フッ素化エーテル類、その組成物、およびその利用
DE102005055811A1 (de) * 2005-11-23 2007-05-31 Novaliq Gmbh Verwendung einer Zusammensetzung zur Konservierung von Organen und Gliedmaßen
EA200870153A1 (ru) * 2006-01-05 2008-12-30 Драгтек Корпорейшн Композиция и способ ее использования
DE102007055046A1 (de) * 2007-11-19 2009-05-28 Fluoron Gmbh Infusionslösung
WO2009111023A2 (en) * 2008-03-04 2009-09-11 Cornell University Triblock polymers and polymer coatings
PT2294044T (pt) * 2008-04-28 2016-09-02 Al Chi Mi A S R L Fluoroalquiloxi-alcanos, processo para a sua produção e suas utilizações
EP2332525A1 (en) * 2009-11-23 2011-06-15 Novaliq GmbH Pharmaceutical composition comprising propofol
EP2335692A1 (en) 2009-12-04 2011-06-22 AL.CHI.MI.A. S.r.l. Silicone liquid and fluorinated liquid for sequential use in the treatment of retinal tears and/or detachments
EP2335735A1 (en) 2009-12-14 2011-06-22 Novaliq GmbH Pharmaceutical composition for treatment of dry eye syndrome
CN102869345B (zh) 2010-03-17 2015-02-11 诺瓦利克有限责任公司 用于治疗眼内压增高的药物组合物
DE202010009243U1 (de) 2010-06-02 2011-09-19 Fluoron Gmbh Zubereitung
DE102010022567A1 (de) * 2010-06-02 2011-12-08 Fluoron Gmbh Zubereitung
EP2444063A1 (en) 2010-10-20 2012-04-25 Novaliq GmbH Liquid pharmaceutical compositions for the delivery of active ingredients
EP2462921A1 (en) 2010-11-11 2012-06-13 Novaliq GmbH Liquid pharmaceutical compositions for the treatment of a posterior eye disease
CN102041142B (zh) * 2010-12-25 2013-11-20 锦州惠发天合化学有限公司 一种含氟润滑油
CN102070493B (zh) * 2011-01-04 2013-07-31 锦州惠发天合化学有限公司 一种含氟润滑油添加剂的制备方法
PT2661280T (pt) * 2011-01-04 2019-02-25 Novaliq Gmbh Emulsões o/a compreendendo alcanos semifluorados
WO2012160180A2 (en) 2011-05-25 2012-11-29 Novaliq Gmbh Pharmaceutical composition for administration to nails
PL2714010T3 (pl) * 2011-05-25 2017-08-31 Novaliq Gmbh Kompozycja farmaceutyczna do miejscowego stosowania oparta na semifluorowanych alkanach
AU2013211645B2 (en) 2012-01-23 2017-06-15 Novaliq Gmbh Stabilised protein compositions based on semifluorinated alkanes
DE102012103097A1 (de) 2012-04-11 2013-10-17 Fluoron Gmbh Färbemittel zum Einfärben einer ophthalmischen Membran
US20130272962A1 (en) 2012-04-11 2013-10-17 Fluoron Gmbh Staining agent for corneal staining
TR201812013T4 (tr) 2012-09-12 2018-09-21 Novaliq Gmbh Göz yikama bi̇leşi̇mleri̇.
EP3181119B1 (en) * 2012-09-12 2019-07-10 Novaliq GmbH Semifluorinated alkane compositions for use in the treatment of keratoconjunctivitis sicca
EP2895158B1 (en) 2012-09-12 2019-11-20 Novaliq GmbH Compositions comprising mixtures of semifluorinated alkanes
KR102285110B1 (ko) 2013-03-13 2021-08-02 산텐 세이야꾸 가부시키가이샤 마이봄 기능부전의 치료제
EP2783703A1 (en) * 2013-03-25 2014-10-01 B. Braun Melsungen AG Semifluorocarbon compound containing contrast agent
US10066186B2 (en) * 2013-04-22 2018-09-04 Basf Se Lubricating oil compositions containing a halide seal compatibility additive and a second seal compatibility additive
JP6109412B2 (ja) 2013-04-22 2017-04-05 ビーエーエスエフ ソシエタス・ヨーロピアＢａｓｆ Ｓｅ 潤滑剤組成物のフルオロポリマーシール適合性を改善させるための、シール適合性添加剤
JP6503349B2 (ja) 2013-07-23 2019-04-17 ノバリック ゲーエムベーハー 安定化された抗体組成物
JP2016535768A (ja) * 2013-11-05 2016-11-17 ソルベイ スペシャルティ ポリマーズ イタリー エス．ピー．エー． 変性炭化水素
EP2944324A1 (de) * 2014-05-13 2015-11-18 LTS LOHMANN Therapie-Systeme AG Verwendung von semifluorierten Alkanen in transdermalen therapeutischen Systemen
WO2016082644A1 (en) * 2014-11-26 2016-06-02 The University Of Hong Kong A semifluorinated alkane based cleaner for removing emulsified droplets in the eye to reduce the complications associated with the emulsification of silicone oil
DE202015101488U1 (de) * 2015-03-24 2016-06-28 Fluoron Gmbh Waschlösung
GB2542406B (en) 2015-09-18 2018-04-11 Schlumberger Holdings Determining properties of porous material by NMR
PT3355990T (pt) 2015-09-30 2019-09-11 Novaliq Gmbh Compostos semifluorados e as suas composições
DE202016008739U1 (de) 2015-09-30 2019-04-29 Novaliq Gmbh Semifluorierte Verbindungen
KR102257916B1 (ko) 2016-06-23 2021-05-28 노바리크 게엠베하 드롭 디스펜서를 포함하는 키트
CN109890374A (zh) 2016-09-22 2019-06-14 诺瓦利克有限责任公司 用于治疗睑缘炎的药物组合物
JP6869336B2 (ja) 2016-09-23 2021-05-12 ノバリック ゲーエムベーハー シクロスポリンを含む眼科用組成物
KR20190060787A (ko) * 2016-09-28 2019-06-03 노바리크 게엠베하 카나비노이드 수용체 결합 리간드를 포함하는 조성물
CN106631681B (zh) * 2016-11-29 2020-07-28 上海杰视医疗科技有限公司 含氟烷烃的纯化方法
WO2018193093A1 (en) 2017-04-21 2018-10-25 Novaliq Gmbh Iodine compositions
WO2018202835A1 (en) 2017-05-05 2018-11-08 Novaliq Gmbh Process for the production of semifluorinated alkanes
CN110650734A (zh) 2017-05-12 2020-01-03 诺瓦利克有限责任公司 治疗与隐形眼镜有关病症的包含半氟化烷烃的药物组合物
US20200339492A1 (en) 2017-06-12 2020-10-29 Novaliq Gmbh Process for the preparation of semifluorinated alkanes using grignard reagents
CN111372566A (zh) 2017-09-27 2020-07-03 诺瓦利克有限责任公司 用于治疗眼部疾病的包含拉坦前列素的眼科用组合物
US11896559B2 (en) 2017-10-04 2024-02-13 Novaliq Gmbh Opthalmic compositions comprising F6H8
WO2019166631A1 (en) 2018-03-02 2019-09-06 Novaliq Gmbh Pharmaceutical compositions comprising nebivolol
JP7496778B2 (ja) * 2018-03-28 2024-06-07 ノバリック ゲーエムベーハー チモロールを含む医薬組成物
US20220079980A1 (en) * 2018-09-27 2022-03-17 Novaliq Gmbh Lipid barrier repair
AU2019345929B2 (en) 2018-09-27 2022-02-03 Dermaliq Therapeutics, Inc. Topical sunscreen formulation
CN112823020A (zh) 2018-10-12 2021-05-18 诺瓦利克有限责任公司 用于治疗干眼病的眼用组合物

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2997505A (en) * 1954-07-12 1961-08-22 Research Corp Fluoro-nitro olefins
DE2060041C3 (de) * 1970-12-05 1973-10-25 Farbwerke Hoechst Ag, Vormals Meister Lucius & Bruening, 6000 Frankfurt Verfahren zur Herstellung von fluorierten Kohlenwasserstoffen
CA1023768A (en) * 1972-12-21 1978-01-03 Horst Jager Polyfluoroalkyl iodides, process for their manufacture, and their use
US4173654A (en) * 1977-01-03 1979-11-06 California Institute Of Technology Novel fluorohydrocarbons
JPS63281218A (ja) * 1987-05-13 1988-11-17 Hitachi Ltd 磁気記録媒体
DE3925525A1 (de) * 1989-08-02 1991-02-07 Hoechst Ag Verfahren zur herstellung von (alpha),omega-bisperfluoralkylalkanen
IT1241402B (it) * 1990-03-02 1994-01-14 Enichem Sintesi Agenti scivolanti
FR2679150A1 (fr) * 1991-07-17 1993-01-22 Atta Preparations comprenant un fluorocarbure ou compose hautement fluore et un compose organique lipophile-fluorophile, et leurs utilisations.
DE4211958A1 (de) * 1992-04-01 1993-10-21 Pharmpur Gmbh Behandlungsmittel für die Augenheilkunde und seine Verwendung

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2110126B1 (de) * 2008-04-18 2011-11-09 Novaliq GmbH Inhalative und instillative Verwendung von semifluorierten Alkanen als Wirkstoffträger im intrapulmonalen Bereich

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DE59604257D1 (de) 2000-02-24
ATE214270T1 (de) 2002-03-15
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CA2473394C (en) 2010-02-09
US6262126B1 (en) 2001-07-17
KR100457157B1 (ko) 2005-04-06
EP0965329A1 (de) 1999-12-22
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DE19536504C2 (de) 1999-09-23
EP0965334A1 (de) 1999-12-22
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US20020198266A1 (en) 2002-12-26
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